Bone as an endocrine organ: the biological role and mechanisms of action of osteocalcin in the vasculature
Lead Research Organisation:
University of Nottingham
Department Name: School of Medicine
Abstract
The mini project will address two aims; (1) what are the direct vascular effects of osteocalcin in human mesenteric arteries, and (2) what are the effects of osteocalcin on endothelial cells.
(1) Using wire myography (O'Sullivan et al., 2004; 2005; 2006; 2009) in human mesenteric arteries we will examine whether osteocalcin causes vasorelaxation of pre-constricted arteries or causes vasoconstriction of arteries when applied to baseline tone. We will also examine physiologically the effect of physiologically-relevant concentrations of osteocalcin on subsequent vasodilator function by exposing arteries to osteocalcin, pre-constricting pharmacologically and then performing concentration responses curves to endothelium-dependent and independent vasorelaxants. The effect of osteocalcin on vasoconstrictor responses to noradrenaline, angiotensin II and endothelin-1 will also be examined.
(2) No studies to date have examined the effects of osteocalcin on endothelial cells, although a recent study suggested that osteocalcin, via hypoxia-inducible factor 1 signalling, stimulates expression of osteochondrogenic transcription factors in VSMCs (Idelevich et al., 2011). Students will investigate the effects of osteocalcin on a human endothelial cell line to establish whether osteocalcin affects a number of features of endothelial cell function, including endothelial cell proliferation (MTT assay), cytotoxicity (LDH assay), the expression of vascular adhesion molecule, vCAM (by ELISA), and markers of calcification (ALP content or calcium staining).
(1) Using wire myography (O'Sullivan et al., 2004; 2005; 2006; 2009) in human mesenteric arteries we will examine whether osteocalcin causes vasorelaxation of pre-constricted arteries or causes vasoconstriction of arteries when applied to baseline tone. We will also examine physiologically the effect of physiologically-relevant concentrations of osteocalcin on subsequent vasodilator function by exposing arteries to osteocalcin, pre-constricting pharmacologically and then performing concentration responses curves to endothelium-dependent and independent vasorelaxants. The effect of osteocalcin on vasoconstrictor responses to noradrenaline, angiotensin II and endothelin-1 will also be examined.
(2) No studies to date have examined the effects of osteocalcin on endothelial cells, although a recent study suggested that osteocalcin, via hypoxia-inducible factor 1 signalling, stimulates expression of osteochondrogenic transcription factors in VSMCs (Idelevich et al., 2011). Students will investigate the effects of osteocalcin on a human endothelial cell line to establish whether osteocalcin affects a number of features of endothelial cell function, including endothelial cell proliferation (MTT assay), cytotoxicity (LDH assay), the expression of vascular adhesion molecule, vCAM (by ELISA), and markers of calcification (ALP content or calcium staining).
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M008770/1 | 01/10/2015 | 31/10/2024 | |||
| 1645180 | Studentship | BB/M008770/1 | 01/10/2015 | 30/09/2019 |
| Description | In the last decade, the skeleton's appreciation as an endocrine organ has significantly increased. Osteocalcin, which is produced by bone cells, gets released into the vascular circulation during bone remodelling that takes place constantly within our bodies. Some epidemiological studies had suggested a link between osteocalcin and cardiovascular disease. We aimed to explore whether there was a direct mode of action of osteocalcin on human vascular cells. We did this by culturing human vascular smooth muscle cells and endothelial cells, and testing actions of osteocalcin in control conditions as well as in inflammatory conditions and other pathological models to represent atherosclerosis and calcification. We discovered that, although osteocalcin could initiate cell signalling responses in vascular cells and promote proliferation, neither a negative or positive role was demonstrated in angiogenesis, inflammation, or calcification. Thus, we concluded that there is no direct role of osteocalcin in cardiovascular disease, however there is an interest in its indirect involvement through interaction with other body systems including glucose metabolism and adipose tissue. |
| Exploitation Route | I don't see any further application other than directing this line of research elsewhere i.e. exploring the interaction of osteocalcin with other body systems/tissues which in turn can affect cardiovascular health and disease. |
| Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |
| Description | Science blog |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | I was in charge of a general interest science blog as part of the STEM outreach Nottingham society. I wrote a few articles and encouraged other students to do the same which I edited and posted, and shared over social media. |
| Year(s) Of Engagement Activity | 2016,2017 |
| URL | https://stemoutreachnotts.wordpress.com/ |
| Description | Science in the Park |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Science in the Park was a Family Fun Day organised by the BSA. We had 3 stands with different activities I was in charge of the DNA origami stand. This involved showing kids how to fold up DNA templates resulting in a DNA double helix! |
| Year(s) Of Engagement Activity | 2016 |
| Description | Talk to general public |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Gave a talk entitled 'The Secret Life of Bones' given at Rough Trade, Nottingham to the general public as part of the launch event for Pint of Science Festival. The talk was loosely based around my PhD area and the interesting functions of bones that are only just being found out such as their hormonal activity. The activity included having a microscope with a bone slide which people could look at. I also had digital interactive slide of a bone section that people could analyse and pick out particular bone cells. We had information leaflets and posters also about bone diseases. |
| Year(s) Of Engagement Activity | 2016 |